Coronaviruses and Immunosuppressed Patients: The Facts During the Third Epidemic

We read with interest the letter by D’Antiga evaluating the early experience with coronavirus disease 2019 (COVID-19) in liver transplantation (LT) recipients in Bergamo, Italy, suggesting that immunosuppression would not increase the risk of severe infections.⁽¹⁾ Another recent report also showed that mortality in LT patients affected by COVID-19 appeared to be limited to longterm (>1 years after LT) recipients with mild immunosuppression and affected by metabolic and vascular comorbidities.⁽²⁾ Even though the pathophysiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still under investigation, the immune system appears to play a major role especially in patients with severe disease,⁽³⁾ thus supporting previous observations.

Between February 21, 2020—the day the first Italian case of COVID-19 was confirmed in Codogno, near Milan—and April 21, 2020, 16 LTs were performed in our center. Regular screening for SARS-CoV-2 was carried out in LT candidates at admission and repeated weekly in hospitalized recipients as well as in all the potential deceased donors. No candidate tested positive at admission, although 2 recipients were diagnosed with COVID-19 (9 and 45 days after LT) and showed an almost asymptomatic course of the infection. The immunosuppressive regimen was left unchanged. Concomitantly, in our preliminary experience, SARS-CoV-2 infection was diagnosed in 5 longterm LT recipients (>1 year after LT) transplanted at our center (>100 transplants/year performed in the last 5 years) who required hospital admission. Among these patients, 2 needed noninvasive ventilation, 2 died due to respiratory failure, and 1 died of septic shock in neutropenia following chemotherapy for lymphoma. Among the 5 patients, 3 patients were affected by diabetes mellitus, 4 were affected by arterial hypertension, and 2 were affected by advanced cancer, supporting a previous report⁽²⁾ on the role of comorbidities in LT recipients with COVID-19. As recently observed,⁽¹⁾ severe immunosuppression, as used in the early posttransplant period, did not appear to negatively affect the outcomes, and calcineurin inhibitors may also partly suppress the innate immune response,⁽⁴⁾ which appears to play a relevant role in the pathophysiology of severe disease in SARS-CoV-2 infection. Nonetheless, because other immunomodulating therapies are emerging in the treatment of COVID-19 (ie, tocilizumab or high-dose steroid), caution is warranted to limit the risk of superimposing bacterial and fungal infections, especially in critically ill patients. Moreover, prompt identification of cases and their management in COVID-19–dedicated areas by a multidisciplinary team can limit the nosocomial spreading of the infection without negatively affecting regular care to hospitalized patients.